Crowd science

First of all, the two problems being addressed...

1) Great ideas are created when several small ideas come together. The
inability to keep up with a wide variety of research will lower the
chances of small ideas coming together. We're having trouble keeping
up with publications in just our own field, so imagine what all useful
discoveries we might be missing from other fields, especially those
obscure journals which might be hiding fragments of a great discovery.

2) Currently, if a curious high school student wants to learn more
about ongoing research, they would have to start reading review papers
or something like that -- this is not very inviting. No wonder the gap
between researchers and public is growing. The current mode of doing research requires a person to go through the PhD 4-6 year ritual. A self-motivated individual does not have sufficient material to become a self-motivated scientist. Even worse, a scientist who wants to cross from one field to another also needs a cross several large barriers.

And now, the solution...

An online game. Imagine a role-playing game where you walk around on
the earth (google earth-like interface with a person walking on it).
As your character walks through regions of the globe, you will see
little signs pop up indicating where the research labs are. There will
also be signs for "schools" (described later). When you click on a
research lab, you see comic strips of up-to-date research -- that's
right, comic strip of what each post-doc, graduate student, and
faculty did that day or any other day. You will also see the data
(graphs, tables, etc.) below each block of the comic strip.

Each comic strip is one line. It starts with a 'mission statement'
(objective or hypothesis) and ends with a concluding statement.
Conclusions can include emoticons, of course. Everything between those
two sentences describes what was was done using pictures and short
descriptions. The comic strips would describe procedures like miniprep
and PCR or even computational steps like parameter fitting. The player
can hover over the comic strip and find "schools" that teach those
concepts. E.g. I would hover over "PCR" step and see several schools
located across the globe that teach what PCR is, with ratings for each
school. Clicking on the schools takes me to online lessons (videos,
etc.) that teach those concepts. Schools with high ratings might even
make money from ads (incentive).

Ok, so now you ask how will these comic strips be generated... with
the Comic Maker of course! Each research lab participating in this
game can download a software called Comic Maker. Comic Maker comes
with hundreds of comic blocks representing some basic procedures. Each comic block can be generates by combining those basic blocks. It will have an easy drag-n-drop interface for creating a pipeline and attaching data to each step of the pipeline. The researcher must start a pipeline using a 'mission statement' and end it using some conclusion, even something as simple as :-( or just a few key words.

More fun stuff: researchers can announce "quests", which are open
problems that they are unable to resolve. Gamers can get involved in
quests. These players have to gather facts from other labs across the
world and generate some solution. They can request the researcher to
perform new experiments for them if they need more data. Similarly,
gamers can create novel hypotheses by collecting results from several
pipelines and present them to researchers.

One key question is: how does this reward the scientists who are in universities? Mainly, the reward is visibility, which is in many cases a big reward. Making research visible is a key for doing good research, and most researchers understand this obvious fact. Of course, placing results in this online game might interfere with the current "publications" approach. The workaround for that problem is simple: just place this in the game after they are published.


That's it. Hopefully that was a fun read. I think it can can be done.
Imagine spending your weekend looking at comics of what everyone is
going at Berkeley instead of going through the procedure section of a
paper. Of course, there will be nice search features, like "find me
everyone who is doing XYZ", where "XYZ" is some sequence of
procedures.

Information vs information carrier

Suppose I write the word "Mango" using pen and paper. Then, suppose I wrote the same word using a chalk and blackboard. It is obvious that I am conveying the same information. The instrument used to convey that information is hardly relevant.

If this analogy can be applied to biological systems, then it is misleading to study physical aspects of signaling separately. Whether the signaling is via transcription factors, enzymes, RNA molecules, small metabolites, or DNA structure, there may not be any relevance with the content of the information that is being delivered by those molecular interactions. Similarly, between-cell communication may not be related to the type of signaling (paracrine, endocrine, quorum sensing, etc.). It might even be possible that the information encoded by molecular interactions is no different that information encoded by cellular interactions.

In summary, it is possible that information in biological systems might come to light if we study the patterns and ignore the physical components that create those patterns. At the same time, the physical aspects are not completely irrelevant. One would not write a book using chalk and blackboard, so the physical aspects of the instruments do restrict the type of information that can be conveyed.

Cell density based effects

In videos such as the one below, the cells in the middle have smaller size and therefore, there are more cells per unit area. This means that the concentration of molecules inside those cells might be different from the concentration of molecules in the cells at the outer boundaries. Suppose the cells have multiple stable states; in such cases, concentration differences can trigger state changes, causing different behavior of the cells based on their location in the colony.

Colonies where density is not equally distributed might use this fact (density dependent state change) to create different roles within the colony. Maybe the state of the cells at the center governs certain aspects of the colony and the state of the cells at the edges governs some other aspect of the colony. Even if evolution has not used this observation as a design strategy, it does not limit us from using the density difference as a design strategy for creating diversity within a population.

Unnoticed evolution of humans

1) Suppose that the microbial community living inside us have a sufficiently long relationship with our own cells such that the microbes have an important role in a large majority of physiological functions, not just digestion.

2) As human societies have evolved, the variety of microbes that live in our environment have undoubtedly changed. Once humans wandered grasslands on bare-foot and ate raw food without even washing them. Now we buy processed food from supermarkets and even walk inside our houses with socks. The result is that the community of microbes that interact with and enter/exit our bodies has changed.

Combining (1) and (2) above leads to the possibility that the human physiology has indeed changed of the past several centuries, even though the change the human phenotype "appears" unchanged. The extent of evolution depends on the extent to which the microbial communities influence human physiology. If there are long-distance signaling molecules that are released by microbes which enter the blood and if the microbes are capable of receiving our signals, then...

Analogy for Protein Bursts

Consider this scenario:

Imagine a store that is open for a certain time interval during the day. In that time interval, several customers rush in to the store. Each customer buys several items. If someone would record the number of items sold as a function of time, he/she would probably observe bursts (one burst = items bought by one person). The time duration for which the store is open will correspond to the number of bursts. In other words, time duration maps to frequency of bursts.

Now, consider this transcription model:

Consider this mechanistic/intuitive model explaining how proteins are produced in bursts and how the frequency of bursts are controlled by the transcription factor:

1. transcription factor binds to promoter regions and opens the region for access by the polymerase

2. the region remains "open" for some time

3. during this time interval, the polymerase may initiate transcription multiple times

4. for each mRNA that the polymerase transcribes, multiple proteins are produced

So, in summary, the transcription factor "opens" the promoter region for the polymerase. Lets assume that upregulating the transcription factor affects the time duration of the "open" promoter. The longer the time interval, the more mRNA will be produced. Each mRNA creates a burst of proteins. Therefore, upregulating transcription factor affects frequency of bursts.

Stochasticity can lead to Stability

While we think of "noise" as a destabilizing force, we actually use noise many times to lead a system to the most stable position. Consider the scenario where you want to get all the items out of a hand bag very quickly; you would hold the bag up-side-down and shake, i.e. add noise. If you just tilt the bag up-side-down, there is a risk that some of the items would get stuck in the bag. Shaking ensures that such temporary "traps" (in mathematical terms, local minima) are avoided. In a sense, this is like stochastic optimization. When all the items are on the floor, they will remain there even if you shake the floor, because that is that is the most stable position.

Perhaps stochasticity in natural systems is a means of "shaking", i.e. a means by which natural systems reach the most stable states and avoid local traps. The most stable state remains relatively stable even at the presence of noise. Consider the situation when all the items from the bag are on the floor -- even shaking the floor would not change the situation significantly. Perhaps this is the nature of the "most stable state" -- it has a wide basin and thus can easily tolerate noise.

Centralized synthetic biology for the community

Vision:

Build a "fun" framework that would attract lots of young minds to ask interesting questions, engineer biological cells to answer those questions, and easily share their results and explanations with each other.

Problem:

1. providing the education to the masses... but I have some hope that young people are quite good are educating themselves, given the motivation

2. Resource

3. Safety

Possible solution:

One or two well maintained centralized robots with a fun interface for entering experiments and storing/visualizing the results. This is very much possible, except that it is expensive. But if the benefit is large enough, it is possible that government and/or companies might solve that issue.

But if such a programmable robot existed as a resource, I can imagine numerous researchers wanting to try new experiments and test new hypotheses. Since the data is centralized, there is a built-in benefit of data-integration, i.e. finding relationships between multiple experiments and drawing conclusions based on large number of experiments. It would be like a Facebook for biological experiments: everyone wants to dump their favorite hypothesis on it.